Our analyses revealed a mosaic of mutations in WNT signaling regulators, including well-known WNT regulators such as RNF43, APC, AXIN2 and ZNRF3. Our analysis identified significant mutual exclusivity between truncating mutations of RNF43 and APC. The mutual exclusivity of mutations in these genes has been previously reported, [8] however it has not been clear whether this mutual exclusivity was, in part, due to the abundance of RNF43 mutations in BRAF mutant cancers, and the relative rarity of APC mutations in this context. This evidence concerns the gene RNF43 and cancer.